The patch reduced pain scores by 29.5% to 32.8% in affected HIV patients, David Clifford, MD, of Washington University in St. Louis, Mo., and colleagues found in a nearly 500-patient clinical trial.

However, placebo spiced up with a tiny, 0.04% concentration of capsaicin to mask randomization produced similar results, they reported here at the Conference on Retroviruses and Opportunistic Infections.

This "unexpectedly potent placebo response" killed the trial and likely any chance of further study of the patch for this indication, Clifford told MedPage Today.

He called the findings disappointing given the promising phase II results.

Because the receptors take a few months to regenerate, this mechanism is assumed to be the reason the skin patch, with its 8% concentration of capsaicin, works against neuropathic pain, Clifford said.

His group randomized 494 patients diagnosed with HIV-related distal sensory polyneuropathy and on a stable pain medication regimen to a single treatment in double-blind fashion with the active control treatment for 30 or 60 minutes or the full-strength capsaicin patch for 30 or 60 minutes.

The patch wrapped around the entire painful area for patients in both groups. All groups received a 60-minute application of 4% lidocaine cream immediately before treatment, "because it hurts so much," Clifford said in an interview.

The researchers had expected to be able to combine the placebo groups. If they did, the pooled patch results would have tended to be superior for the primary endpoint of Numeric Pain Rating Scale scores reduction sustained over follow-up weeks two to 12 compared with controls (-29.5% versus -24.6%, P=0.1020).

But the two placebo application durations produced substantially different responses: a 30.1% reduction in pain score in the 60-minute group compared with a 19.1% reduction in the 30-minute group.

For the 30-minute application comparisons, the 8% capsaicin treatment tended to reduce pain score more than the 0.04% capsaicin control (-26.1% versus -19.1%, P=0.1032).

For the 60-minute application comparisons, the full-strength patch was no better than its control (-32.8% versus -30.1% pain score change, P=0.5125).

Subjective assessment of at least "slight" improvement in the painful condition indicated a treatment benefit overall in the combined capsaicin groups (P=0.0106) and in the 30-minute application capsaicin group (P=0.0057) compared with controls.

Not surprisingly, the most common adverse events reported with the capsaicin patch were transient pain at the treatment site and erythema.

However, most patients tolerated capsaicin treatment well, with 97% completing at least 90% of intended patch duration, the investigators noted.

This condition still has no approved treatments, with an earlier study testing pregabalin (Lyrica) also having failed due to a strong placebo effect, Clifford noted.